Overview of developmental heart defects by dioxins, PCBs, and pesticides.

The developing cardiovascular system is a sensitive target of many environmental pollutants, including dioxins, dioxin-like polychlorinated biphenyls (PCBs), and some pesticides such as methyl parathion. Laboratory research has utilized a variety of vertebrate models to elucidate potential mechanisms that mediate this cardioteratogenicity and to establish the sensitivity of different species for predicting potential risk to environmental and human health. Studies of dioxin and dioxin-like PCBs have illustrated that piscine, avian, and mammalian embryos exhibit cardiovascular structural changes and functional deficits, although the specific characteristics vary among the individual models. Piscine models typically exhibit reduced blood flow, altered heart looping, and reduced heart size and contraction rate. The chick embryo exhibits extensive cardiac dilation, thinner ventricle walls, and reduced responsiveness to chronotropic stimuli, while the murine embryo exhibits reduced heart size. It is notable that in all models the dioxin-associated cardioteratogenicity is associated with increases in cardiovascular apoptosis and decreases in cardiocyte proliferation. While the cardiotertogenicity in piscine and avian species is associated with overt morbidity and mortality, that is not the case for the murine embryo. However, murine offspring exposed during development to dioxin exhibit cardiac hypertrophy and an increased sensitivity to a second cardiovascular insult in adulthood. Thus, although the mammalian embryo is less sensitive to cardiovascular defects by dioxin and dioxin-like compounds, developmental exposure increases the risk of cardiovascular disease later in life. The impact of developmental exposure to dioxin-like chemicals on human cardiovascular disease susceptibility is not known. However, recent animal research has confirmed human epidemiology studies that dioxin exposure in adulthood is associated with hypertension and cardiovascular disease.